Improved Survival and Neurological Outcomes after Cardiopulmonary Resuscitation in Toll-like Receptor 4-mutant Mice / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 2646-2651, 2015.
Article
in En
| WPRIM
| ID: wpr-315279
Responsible library:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>Toll-like receptor 4 (TLR4) is a crucial receptor in the innate immune system and noninfectious immune responses. It has been reported that TLR4 participates in the pathological course of ischemia/reperfusion (I/R) injury. However, the role of TLR4 in the process of I/R injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) is still unknown. In this study, we investigated the effects of TLR4 mutation on survival and neurological outcome in a mouse model of CA/CPR.</p><p><b>METHODS</b>A model of potassium-induced CA was performed on TLR4-mutant mice (C3H/HeJ) and wild-type mice (C3H/HeN). After 3 min of untreated CA, resuscitation was attempted with chest compression, ventilation, and intravenous epinephrine. Behavioral tests were performed on mice on day 3 after CPR. The morphological changes in hippocampal neurons were assessed by light and electron microscopy. Expressions of TLR4 and intercellular adhesion molecule-1 (ICAM-1) were detected by Western blot. Levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were measured with enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>On day 3 after resuscitation the overall mortality was 33.33% in C3H/HeJ group compared with 53.33% in C3H/HeN group (P < 0.05). And there was much higher central tendency in C3H/HeJ group than C3H/HeN group during open field test (P < 0.05). Meanwhile, the percentage of nonviable neurons was 21.16% in C3H/HeJ group compared with 53.11% in C3H/HeN group (P < 0.05). And there were significantly lower levels of hippocampal TNF-α and MPO in C3H/HeJ mice (TNF-α: 6.85±1.19 ng/mL, MPO: 0.33±0.11 U/g) than C3H/HeN mice (TNF-α: 11.36±2.12 ng/mL, MPO: 0.54±0.17 U/g) (all P < 0.01). CPR also significantly increased the expressions of TLR4 and ICAM-1 in C3H/HeN group. However, the expression of ICAM-1 was much lower in C3H/HeJ group than in C3H/HeN group after CPR (P < 0.01).</p><p><b>CONCLUSION</b>TLR4 signaling is involved in brain damage and in inflammation triggered by CA/CPR.</p>
Full text:
1
Database:
WPRIM
Main subject:
Therapeutics
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Brain
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Blotting, Western
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Tumor Necrosis Factor-alpha
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Cardiopulmonary Resuscitation
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Peroxidase
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Intercellular Adhesion Molecule-1
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Allergy and Immunology
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Toll-Like Receptor 4
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Genetics
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Chinese Medical Journal
Year:
2015
Document type:
Article